Project Summary: Hopkins Clinical Center for Pulmonary Vascular Disease Phenomics Program The Hopkins Pulmonary Hypertension (PH) program is composed of a highly dedicated, multi-disciplinary group of experts from various institutional divisions and departments, who have a long history of close interaction and rich productivity within the framework of current and previous NIH-supported research projects. Our Program primarily provides comprehensive management of patients from all five groups of the PH World Classification, and also has a long history of participation in industry-sponsored as well as NIH-sponsored multicenter clinical trials for PH treatment. Since right ventricular (RV) function is the main determinant of death in PH, we propose thorough phenotyping of PH patients with a primary focus on the complex relationship between the RV and the pulmonary vasculature (PV) and RV-PV uncoupling, with the goal to further examine their crucial impact on morbidity and mortality in PH. Leveraging our extensive clinical knowledge in PH and our expertise in molecular and diagnostic pulmonary medicine and cardiology, we propose to use 1) echocardiography and cardiac magnetic resonance imaging (cMRI) to identify non-invasive measures of RV performance and their capacity to predict outcomes; 2) invasive hemodynamic assessment of RV/PV interaction for its impact on deep phenotyping and survival; and 3) molecular (genomics, genetics, and serum biomarkers) for endophenotyping. The search for clinical, hemodynamic, imaging, serum and genetic biomarkers proposed in this application can be readily applied to all clinical centers in the context of the PVDOMICs as relevant variables for disease risk assessment, dynamic phenotyping (baseline and in response to treatment), endophenotyping, and as intermediate or primary outcomes in clinical trials. In summary, while the choice of parameters, studies and target populations will be left to the discretion of the DCC, our PH clinical center will offer the unique expertise of a multidisciplinary and highly integrated team of experts in this new endeavor to redefine PH phenotypes from all five groups of PH, thus ensuring success of the PVDOMICs efforts.